PATHOPHYSIOLOGY MODULE 09: FLUID AND ELECTROLYTE BALANCE STUDY GUIDE

Prevention of HIV infection:  Anti-retroviral therapies do not represent a cure for HIV, hence prevention of HIV infection is key.  Prevention largely involves avoiding high risk behaviours and utilizing appropriate protective measures to prevent HIV transmission. In all of this, education of risk factors and safe practices is paramount - Abstinence/monogamy o Avoid sex with multiple partners o Avoid unprotected sex o Proper and consistence use of condoms - Avoid other high risk behaviours o Recreational IV drug use o Other drug use o Observe universal blood and body fluid precautions o Breast feeding when infected Cancer and cancer terminology  Neoplasm or neoplastic means new growth. Any abnormal growth of new tissue is referred to as neoplastic.  Neoplastic growth and tumor are two terms used interchangeably.  Benign describes a non-cancerous tumor growth and malignant describes cancerous tumor growth.  Cancer is the uncontrolled growth of abnormal cells in the body  Cancerous cells are also called malignant cells (the term cancer is used interchangeably with the term “malignancy”)  Malignant/cancerous cells are composed of less well-differentiated cells that have lost the ability to control both cell proliferation and differentiation into a mature cell  Cancer is not a single disease. The term cancer as we know it applies to numerous diseases with more than 200 types of cancer having been identified  Oncology – the study of tumours and their treatment; includes benign and malignant tumours Incidence and mortality rates  Cancer is the leading cause of death worldwide and in Canada and accounts for 13% of all deaths worldwide and 30% of deaths in Canada  The prevalence of cancer in Canada is high due to the rising number of cancer diagnoses and improvements in detection and survival  An estimated 39% of Canadian females and 45% of males will develop cancer in their lifetime - Prostate cancer in men (29%) and breast cancer in women (26%) account for the highest proportion of new cases, followed by lung and bronchus cancers (15%) and colon and rectum cancers (10-11%). Together, these account for over 50% of all new cases - Across Canada, rates of cancer incidence vary due to variation in risk factors and early detection of cancer. However, overall, an estimated 177,800 new cancers (excluding non-melanoma skin cancers) will occur in Canada in 2011  An estimated 24% of women, and 29% of men will die from Canada (approx. 1 in 4) - Lung and bronchus cancers account for the most cancer related deaths in both genders (31% men; 26% women), followed by prostate (9%) and breast cancers (15%) in males and females respectively, National cancer care expenditures have been steadily increasing. In 2006, cancer care accounted for an estimated 104.1 billion dollars in medical care expenditures in the United States alone.  Direct medical expenditures are only one component of the total economic burden of cancer. The financial costs of cancer care are a burden to the people diagnosed with cancer, their families and society as a whole. The indirect costs include losses in time and economic productivity resulting from cancer related illness and death The cell cycle and carcinogenesis  The normal cell cycle:  The cell cycle is the sequence of events involved in the replication and distribution of DNA to daughter cells. In a complete cell cycle, a starting cell duplicates its contents and divides into identical daughter cells. Thus, the cell cycle functions to allow for the process of cell proliferation, i.e. as the cells duplicate, there is an increase in the number of cells  Phases of the normal cell cycle: - G1: the cell enters the cell cycle and begins the process of getting ready to divide. In this phase, he cell is metabolically active or growing, and is creating enzymes of proteins in preparation for DNA synthesis - S phase: during s-“synthesis” phase, the DNA is synthesized and chromosomes are replicated (this is one of the “major phases” of the cell cycle) - G2: is the second growth phase. Again, the cell is metabolically active or growing, and is creating enzymes of proteins in preparation for mitotic division. - M phase: the cell divides and two daughter cells are formed - The duration of the M, G2, and S phases is relatively constant; whereas the time a cell spends in G1 varies (depending on cell type) from a few hours to several days. This determines the overall length of the cell cycle.  After mitosis, the daughter cells either go into a state of dormancy, i.e. the G0 phase where they are not actively proliferating, or if a stimulus for cell division exists, the cell enters the G1 phase to begin the cell reproductive cycle again  All cells, malignant or non-malignant, progress through the 5 phases of the cell cycle – G0, G1, S, G2 and M. However, cancer cells are able to complete the cell cycle more quickly, by decreasing the length of time spent in the G1 phase. They are also much less likely to enter or remain in the G0 phase  Differentiation and Proliferation  As the cell divides and increases in number, the resulting daughter cells organize and become differentiated. Cell differentiation is the process by which proliferating cells become specialized. This is an orderly process with increasing specialization occurring with each step - For example, immature cells differentiate into mature skin cells or immature cells differentiate into 2. Labile cells rapidly regenerate. These cells that continue to proliferation and then die, particularly in areas that have a high cell turnover – e.g. GI tract, blood cells, skin cells. These are known as progenitor cells 3. Stem cells can enter the cell cycle and produce progenitor cells when required. The stem cell can remain quiet/dormant until needed and then be called upon to produce daughter cells of the type required (specialized). Think of the stem cell as a cell from which other types of cell develop. o A stem cell transplant is a method of replacing cancerous bone marrow with healthy stem cells. After the diseased marrow is destroyed by chemo and radiation, stem cells are injected into the patient and these stem cells go on to proliferate into healthy blood cells. An allogeneic transplant entails receiving a donor’s stem cells. An otologist transplant entails receiving one’s own stem cells.  Cell cycle checkpoints:  In most cells, there are several checkpoints in the cell cycle, at which time the cycle can be stopped if previous events have not been completed - These checkpoints are actually a series of processes and proteins that help regulate cell damage and repair. These include apoptosis, the DNA repair system, and tumour suppressor genes.  The G1-S checkpoint monitors whether DNA in the chromosomes is damaged by radiation or chemicals (i.e. is DNA appropriate for replication?)  The G2-M checkpoint prevents entry into mitosis if DNA replication is not complete (i.e. is the DNA appropriate for incorporation into daughter cells?) - Although each phase of the cell cycle is monitored carefully, the transition from G2 to M is believed to be one of the most important checkpoints in the cell cycle Carcinogenesis  Biologists estimate that more than 100 million billion cells must cooperate to keep a human being healthy over the course of an 80-year lifespan. Normal cells in the body follow an orderly path of growth, division and death. In order to keep these cells growing in a controlled and programmed fashion, it involves a series of complex molecular processes  Cancer is a disease in which a single normal body cell undergoes a genetic transformation into a cancer cell. This cell and its descendants proliferating across many years produce the population of cells that we recognize as a tumor. Seven warning signs of cancer: 1. Change in bowel/bladder habits 2. A sore that doesn’t heal 3. Unusual bleeding or discharge 4. Thickening of lump in breast, testicles or elsewhere. 5. Indigestion or difficulty swallowing 6. Obvious change in size, colour, shape or thickness of wart, mole or mouth sore 7. Nagging cough or hoarseness